Condensation products of tetramethylenediamine with hydrogenated fatty acids of castor-oil

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Type of information:

other: expert statement

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Expert statement based on a series of physicochemical and toxicology studies with WS405777, in general, performed according to technical guidelines and in compliance with GLP in internationally recognized contract research organizations.

Objective of study:

absorption

Qualifier:

no guideline required

Principles of method if other than guideline:

Expert statement based on a series of physicochemical and toxicology studies with WS405777. Technical guidelines followed in these experimental studies are cited in the respective endpoint study records.

GLP compliance:

no

Remarks:

Considered unnecessary for expert statement

Executive summary:

No specific study was performed on the absorption, distribution, metabolism and/or excretion (ADME) of WS405777. WS405777 has a rather high molecular weight (653 Da), extremely low water solubility (2 x10-9 mg/L, calculated for the main component) and extreme hydrophobicity (Log10Kow = 12.3 calculated for the main component). These properties would be expected to limit its absorption across the skin after topical administration and also to limit its absorption after oral administration [ECHA, Chapter R.7c: Endpoint specific guidance]. Consequently these physical-chemical properties of WS405777 are considered to limit its systemic availability both, after topical and after oral administration. This is consistent with the absence of signs of an irritation potential in an in vitro skin irritation study and in the Local Lymph Node Assay (LLNA) in mice and with the absence of any sensitization response in the latter study. In addition, in a repeat dose oral toxicity study combined with reproductive/developmental toxicity screening, in which rats received WS405777 at 100, 300 or 1000 mg/kg/day, findings clearly indicative of absorption were not evident after 4 treatment weeks; the NOAEL was derived at the highest dose level for all endpoints.

No data is available on absorption after inhalation. Due to its low vapour pressure (2 x 10E-6 Pa at 25°C), WS405777 is unlikely to be available under a vapour state. Exposure of humans to inhalable particles of WS405777 is also unlikely. After manufacture of the condensation product, WS405777 in a dedicated facility is micronized in a ball mill under rigorous containment. The micronized substance then is dispersed in an organic solvent to form a paste. Only the paste-form is marketed. The substance in paste-form is used only at industrial sites and added to surface coating systems and thus finally is incorporated into a polymer matrix.

Due to absence of adverse effects in all studies, it is not known if the substance is absorbed and becomes systemically available. Accordingly, no information is available on distribution, metabolism and excretion.

Based on the available data the bioacumulation potential cannot be judged. However, based on the favourable testing results, i.e. low toxicological potential, on the one hand and on the very low dermal and inhalative bioavailability of the substance (due to its physical-chemical properties) on the other hand there is no need for further investigations of a bioaccumulation potential.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

No specific study was performed on the absorption, distribution, metabolism and/or excretion (ADME) of WS405777. WS405777 has a rather high molecular weight (653 Da), extremely low water solubility (2 x10-9 mg/L, calculated for the main component) and extreme hydrophobicity (Log10Kow = 12.3 calculated for the main component). These properties would be expected to limit its absorption across the skin after topical administration and also to limit its absorption after oral administration [ECHA, Chapter R.7c: Endpoint specific guidance]. Consequently these physical-chemical properties of WS405777 are considered to limit its systemic availability both, after topical and after oral administration. This is consistent with the absence of signs of an irritation potential in an in vitro skin irritation study and in the Local Lymph Node Assay (LLNA) in mice and with the absence of any sensitization response in the latter study. In addition, in a repeat dose oral toxicity study combined with reproductive/developmental toxicity screening, in which rats received WS405777 at 100, 300 or 1000 mg/kg/day, findings clearly indicative of absorption were not evident after 4 treatment weeks; the NOAEL was derived at the highest dose level for all endpoints.

No data is available on absorption after inhalation. Due to its low vapour pressure (2 x 10E-6 Pa at 25°C), WS405777 is unlikely to be available under a vapour state. Exposure of humans to inhalable particles of WS405777 is also unlikely. After manufacture of the condensation product, WS405777 in a dedicated facility is micronized in a ball mill under rigorous containment. The micronized substance then is dispersed in an organic solvent to form a paste. Only the paste-form is marketed. The substance in paste-form is used only at industrial sites and added to surface coating systems and thus finally is incorporated into a polymer matrix.

Due to absence of adverse effects in all studies, it is not known if the substance is absorbed and becomes systemically available. Accordingly, no information is available on distribution, metabolism and excretion.

Based on the available data the bioacumulation potential cannot be judged. However, based on the favourable testing results, i.e. low toxicological potential, on the one hand and on the very low dermal and inhalative bioavailability of the substance (due to its physical-chemical properties) on the other hand there is no need for further investigations of a bioaccumulation potential.